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PubMed1999

Severe uvular angioedema caused by intranasal administration of Ecbalium elaterium.

A 54-y-o woman presented to the Emergency Department with shortness of breath and sore throat after intranasal administration of Ecbalium elaterium as a folk remedy for her sinusitis. The patient's history included nasal aspiration of the juice of the squirting cucumber (Ecbalium elaterium) for acute maxillary sinusitis. An airway obstruction due to severe uvular angioedema was detected and confirmed by airway X-ray. The patient was treated with 100% oxygen with mask, 0.3 mg epinephrine s.c., and 80 mg prednisolone i.v. Renal and hepatic function tests were normal. After a 24-h observation, the patient was discharged in her previous state of health.

Administration, Intranasal↗

PubMed1999

Intranasal administration of diazepam aiming at the treatment of acute seizures: clinical trials in healthy volunteers.

Intranasal administration of diazepam may be a practical alternative to the conventional acute medication of seizures, such as status epilepticus. Nine healthy students participated in an open crossover study on intranasal versus intravenous administration of diazepam (2 mg). Blood samples were collected, pharmacodynamic tests were performed, and the volunteers filled out questionnaire. Peak concentration was achieved after 18+/-11 min and the bioavailability was 50.4+/-23.3%. A pharmacodynamic effect was observed after about 5 min, but the dose, even for i.v. administration, was too low to generate a strong measurable effect. The results indicate that intranasally administered diazepam may be an effective alternative to i.v. administration in relief of seizures, e.g. in an acute situation when a physician or nurse is not available on location.

Administration, Intranasal↗

PubMed1997

Intranasal administration of Schistosoma mansoni adult worm antigen in combination with cholera toxin induces a Th2 cell response.

Mice immunized with soluble adult worm antigen (SWAP) in combination with cholera toxin (CT) displayed significantly larger numbers of IgG1, IgM and IgA secreting cells in the spleen and in the lungs as compared to mice which had received SWAP only. The ratio of SWAP-specific IgG1 to IgG2a antibody-secreting spleen cells was also significantly higher in the SWAP-CT group. Analysis of cytokine responses revealed that SWAP-stimulated spleen and lung cells from the SWAP-CT group produced lower levels of IFN-gamma but higher levels of IL-4 and IL-5 as compared to cells from the SWAP group. These findings indicate that intranasal administration of SWAP-CT induces a Th2 cell response in the spleen and in the lungs. Our findings also suggest that CT was responsible for induction of this Th2 cell response, since intranasal administration of SWAP alone induced a Th1 type response in the spleen and in the lungs.

Administration, Intranasal↗

PubMedDate not supplied

The influence of glycoprotein hormones selected properties of selected properties of glycoprotein hormones on their absorption after intranasal administration in foxes.

The absorption of glycoprotein hormones, i.e. folitropin and lutropin, whose approximate molecular weight is 30,000 D, were estimated for the intranasal administration. The maximal hormone concentrations were observed 30 minutes after their administration. The maximal concentration of folitropin was 32% higher than the maximal concentration of lutropin. Bioavailability level for foliotropin was 138.58% compared to lutropin bioavailability level, which was considered the pattern bioavailability level (100%) in our experiments. It was established that the absorption of hormones from nasal mucous membrane depended not only on their molecular mass but also on the isoelectric point, content of carbohydrates and sialic acids. Hormonal substances of acid character, containing a greater content of carbohydrates and sialic acids (as in the case of folitropin) were absorbed from the nasal mucosa more rapidly.

Absorption↗

PubMed2007

Response of calves to challenge exposure with virulent bovine respiratory syncytial virus following intranasal administration of vaccines formulated for parenteral administration.

OBJECTIVE: To determine whether single-fraction and combination modified-live bovine respiratory syncytial virus (BRSV) vaccines commercially licensed for parenteral administration could stimulate protective immunity in calves after intranasal administration. DESIGN: Randomized controlled trial. ANIMALS: 39 calves. PROCEDURES: Calves were separated from dams at birth, fed colostrum with a minimal concentration of antibodies against BRSV, and maintained in isolation. In 2 preliminary experiments, 9-week-old calves received 1 (n = 3) or 2 (3) doses of a single-component, modified-live BRSV vaccine or no vaccine (8 control calves in each experiment), and were challenged with BRSV 21 days after vaccination. In a third experiment, 2-week-old calves received combination modified-live virus (MLV) vaccines with or without BRSV and calves were challenged with BRSV 8 days later. Calves were euthanized, and lung lesions were measured. Immune responses, including serum and nasal antibody and nasal interferon-alpha concentrations, were assessed. RESULTS: BRSV challenge induced signs of severe clinical respiratory tract disease, including death and pulmonary lesions in unvaccinated calves and in calves that received a combination viral vaccine without BRSV. Pulmonary lesions were significantly less severe in BRSV-challenged calves that received single or combination BRSV vaccines. The proportion of calves that shed virus and the peak virus titer was decreased, compared with control calves. Protection was associated with mucosal IgA antibody responses after challenge. CONCLUSIONS AND CLINICAL RELEVANCE: Single and combination BRSV vaccines administered intranasally provided clinical protection and sparing of pulmonary tissue similar to that detected in response to parenteral delivery of combination MLV and inactivated BRSV vaccines previously assessed in the same challenge model.

Administration, Intranasal↗

PubMed1997

Intranasal administration of the dopaminergic agonists L-DOPA, amphetamine, and cocaine increases dopamine activity in the neostriatum: a microdialysis study in the rat.

The effectiveness of intranasal drug administration to stimulate central neuronal systems is well known from drug addiction and has also been considered as an alternative pharmacokinetic approach to treat brain disorders such as Parkinson's disease. In the present study, the possible neurochemical effects of intranasal administration of the psychostimulants cocaine and amphetamine and of the antiparkinsonian drug L-DOPA were analyzed. By using in vivo microdialysis in the urethane-anesthetized rat, it was found that unilateral intranasal administration of either of the psychostimulants led to huge and rapid increases of extracellular dopamine levels in the neostriatum followed by decreases of its metabolites dihydroxyphenylacetic acid and homovanillic acid. Furthermore, intranasal administration of L-DOPA, but not of the saline vehicle, also led to increased extracellular levels of neostriatal dopamine and to increases of its metabolites. Because the effect of intranasal L-DOPA on neostriatal dopamine was observed only ipsilaterally but not contralaterally to the side of intranasal drug administration, it can be hypothesized that L-DOPA was not effective via passage through the circulation but may have acted through a neuronal or an extraneuronal route. These data provide neurochemical evidence that the intranasal route may not only be efficient in drug abuse, but may also be useful to target the brain therapeutically, as in the case of neurodegenerative brain disorders.

Administration, Intranasal↗

PubMed1992

Efficacy of once-a-day intranasal administration of triamcinolone acetonide in patients with seasonal allergic rhinitis.

A 4-week, double-blind, parallel group study compared the safety and efficacy of once-a-day intranasal administration of triamcinolone acetonide (Nasacort) versus placebo in 304 patients (155 adult and 149 adolescent) with seasonal allergic rhinitis. Patients were randomized to receive triamcinolone acetonide (110, 220, or 440 microgram) or placebo once daily each morning. Daily rhinitis symptoms scores, weekly patient and physician global assessments, and weekly nasal eosinophil smears were obtained. In each triamcinolone acetonide group, significant (P less than .05) improvement over placebo was noted in the nasal index (sum of ratings for stuffiness, discharge, and sneezing) by week 1, the first point of analysis, and maintained throughout the study. Triamcinolone acetonide groups also demonstrated significant (P less than .05) improvement over placebo in all individual rhinitis symptoms evaluated. The greatest improvement in symptoms was observed at the 440 microgram dose. A significant decrease in eosinophil counts paralleled clinical improvement in all triamcinolone acetonide groups. Physicians and patients rated triamcinolone acetonide significantly (P less than .05) more effective than placebo. Responses of adult and adolescent patients were comparable. Adverse experiences, clinical laboratory values, and results of physical examinations were unremarkable and comparable between the triamcinolone acetonide and placebo groups. We conclude that triamcinolone acetonide is safe, well tolerated, and superior to placebo as a once-a-day treatment for seasonal allergic rhinitis.

Administration, Intranasal↗

PubMed2005

Increased microglial activation and astrogliosis after intranasal administration of kainic acid in C57BL/6 mice.

Glutamate excitotoxicity plays a key role in inducing neuronal cell death in many neurological diseases. In mice, intranasal administration of kainic acid (KA), an analogue of the excitotoxin glutamate, results in hippocampal cell death and provides a well-characterized model for studies of human neurodegenerative diseases. In this study, we describe neurodegeneration and gliosis following intranasal administration of KA in C57BL/6 mice. By using Nissl's staining, neurodegeneration was found in area CA3 of hippocampus, and neuronal apoptosis was demonstrated by enhanced FAS(CD95/APO-1) expression detected by immunohistochemistry and Western blotting. Astrogliosis was exhibited by increased glial fibrillary acidic protein (GFAP) expression in the hippocampus and cortex. We also studied the profile of molecular expression on microglia in C57BL/6 mice. One and 3 days after KA administration, CD45, F4/80, CD86, MHCII, iNOS but not CD40 expression was enhanced or induced on microglia. In summary, KA administration results in an early microglial activation and a prolonged astrogliosis in C57BL/6 mice.

Animals↗

PubMed2004

Brain uptake of the glucagon-like peptide-1 antagonist exendin(9-39) after intranasal administration.

Exendin, a member of the glucagon-like peptide-1 family, and its antagonist exendin(9-39) affect cognition and neuronal survival after their intranasal delivery. Here, we examined the uptake of radioactively labeled exendin(9-39) (I-Ex) by the olfactory bulbs, brain (minus pineal, pituitary, and olfactory bulb), cerebrospinal fluid, and cervical lymph nodes (C-node) as well as levels in serum after intranasal or intravenous administration. We found that olfactory bulb uptake of I-Ex after intranasal administration was rapid, much greater than after i.v. administration, and was enhanced by about 60% with cyclodextrin (CD). I-Ex was also taken up by the remainder of the brain after intranasal administration, but this uptake was not enhanced by CD, nor did it exceed uptake after i.v. administered I-Ex. Uptake by the olfactory bulb was not dependent on Brownian motion but did involve active processes. Intranasal I-Ex reached the C-node by way of the blood. About one-sixth of the intranasal dose of I-Ex entered the blood. However, the vascular route accounted for little of the intranasal I-Ex that reached the brain and even less that reached the olfactory bulb. I-Ex after intranasal administration was found in the hippocampus, cerebellum, brain stem, and cerebrospinal fluid (CSF). Distribution patterns showed that intranasal I-Ex used the extraneuronal route of CSF rather than brain parenchyma to diffuse throughout the brain. These results show that intranasal administration is an effective means of delivering peptide to the brain, especially the olfactory bulb.

Administration, Intranasal↗

PubMed1993

Comparison of GH-stimulation by GH-RH(1-29)NH2 and an agmatine29 GH-RH analog, after intravenous, subcutaneous and intranasal administration and after pulmonary inhalation in rats.

Many studies have shown that human GH-RH(1-29)NH2 possesses full intrinsic activity of GH-RH(1-44)NH2 in vitro and in vivo. This investigation was performed to evaluate the efficacy of GH-RH(1-29)NH2 given by different routes of administration in stimulating GH release in rats. In each case GH-RH(1-29)NH2 was administered intravenously, subcutaneously, intranasally and by pulmonary inhalation at two different doses to groups of seven males rats. At a dose of 150 micrograms/kg GH-RH(1-29)NH2, the magnitude of GH response was significantly higher for the pulmonary inhalation group (355 +/- 33.2 ng GH/mL) than for the subcutaneous group (246 +/- 36 ng GH/mL) or for the intranasal group (175 +/- 30 ng GH/mL). The group injected intravenously with GH-RH(1-29)NH2 at a dose of 2.5 micrograms/kg showed the highest response, GH levels reaching 877.2 +/- 115 ng/mL. A similar pattern of responses was obtained for the superactive GH-RH(1-29) agmatine29 analog, MZ-3-149, at doses that were 50 times lower. Our results indicate a high bioavailability of GH-RH(1-29)NH2 or analog MZ-3-149 administered by a convenient pulmonary inhalation route. The GH-releasing effect of GH-RH(1-29)NH2 or analog MZ-3-149 delivered by pulmonary inhalation is superior to subcutaneous and intranasal administration.

Administration, Inhalation↗

PubMed1991

Plasma concentrations of midazolam in children following intranasal administration.

Nasally administered midazolam appears to be a useful method for rapidly sedating children prior to the induction of anesthesia. We determined the peak plasma concentrations after intranasal administration of midazolam and compared this to plasma concentrations achieved after intravenously administered midazolam in 18 children between the ages of 14 months and 5 yr, who underwent elective closure of an asymptomatic atrial septal or ventricular septal defect. Preanesthetic medication was at the discretion of the attending anesthesiologist. Induction of anesthesia was with halothane in N2O and O2 via mask, and tracheal intubation was performed after the administration of fentanyl or sufentanil plus pancuronium. Anesthesia was maintained with these agents, and augmented with halothane or isoflurane. As soon as arterial access was established, the patient received 0.1 mg/kg of either intranasal or intravenous midazolam. Midazolam concentrations were measured by gas chromatography-mass spectrometry. Intranasal midazolam achieved its peak plasma concentration of 72.2 +/- 27.3 ng/ml in 10.2 +/- 2 min. Ten minutes after the administration of midazolam, the mean plasma concentration in the intranasal midazolam group was 57% of the concentrations in the group receiving midazolam intravenously. These results confirm the clinical impression that intranasal administration of midazolam rapidly achieves sedative plasma concentrations in children.

Administration, Intranasal↗

PubMed2004

Adaptive behavior in active and passive rats after intranasal administration of corticotrophin-releasing hormone.

Rats with high (KHA) and low (KLA) rates of acquiring active avoidance reflexes were used to study the effects of intranasal administration of corticotrophin-releasing hormone on orientational-investigative behavior in an open field and anxiety in an elevated cross maze. Administration of the neurohormone induced opposite changes in the behavior of the rats of these lines in the two tests. In KLA rats, movement and investigative activity increased, while in KHA rats these behaviors decreased. In the elevated maze, KLA rats, unlike KHA rats, showed increases in the time spent in the open arms, which was evidence for a decrease in anxiety in these animals. Thus, intranasal hormone administration completely reproduced the effects seen after administration into the striatum. It is suggested that corticotrophin-releasing hormone is an endogenous factor for the detailed and appropriate correction of adaptive behavior.

Adaptation, Psychological↗

PubMed1997

Local transient induction of inflammatory cytokines after intranasal administration of recombinant Bordetella pertussis.

Inflammatory cytokines have been described to play a critical role in the orientation and amplification of the IgA immune response. In this study, we show that the intranasal administration of a Bordetella pertussis strain expressing the protective antigen glutathione-S-transferase of Schistosoma mansoni (Sm28GST) induced an inflammatory response in the lungs of mice, characterized by the production of inflammatory cytokines, such as Tumor Necrosis Factor alpha, Interleukin-6 and Transforming-Growth Factor beta. The production and the secretion of these cytokines in lung tissues were early and transient. Their presence was observed only during the first week after administration despite the persistence of the bacteria for 1 month. Two weeks after inoculation, Interleukin-10 secretion was detected in the lungs, which could explain the decrease in the production of inflammatory cytokines. These inflammation-regulating cytokines, induced in the lungs by the presence of the bacterial vector, could be part of the process generating the local immune response, in particular the anti-Sm28GST IgA response.

Administration, Intranasal↗

PubMed2005

Studies on the in vivo hypoglycemic activities of two medicinal plants used in the treatment of diabetes in Jordanian traditional medicine following intranasal administration.

The claimed hypoglycemic activities of Paronychia argentea Lam. (Caryophyllaceae) and Teucrium polium L. (Labiatae), two traditionally widely used medicinal plants in Jordan were evaluated using normoglycemic and alloxan induced hyperglycemic rabbits by intranasal administration of the plant crude extracts (10%) in a vehicle containing 5% (w/w) Pluronic F127. No significant difference was observed between the extract treated and non-treated control animals receiving only water.

Administration, Intranasal↗

PubMed1995

[Influence of intranasal administration on calcitonin consumption].

OBJECTIVE: An analysis of the impact of the commercialisation of intranasal administration on calcitonin consumption. DESIGN: Descriptive study. SETTING: Non-hospital ambit within the national health system. PATIENTS AND OTHER PARTICIPANTS: A protected population group within the national health system, with occupationally active people and pensioners being differentiated. INTERVENTIONS: Commercialisation of a new way of administering calcitonins in March 1992. MEASUREMENTS AND MAIN RESULTS: The consumption of calcitonins dispensed in prescriptions by the national health system was differentiated according to methods of administration; calculations being made for the number of containers, cost and daily dosage defined (DDD) by population groups (overall and pensioners) and for the distribution of consumption for Autonomous Communities in DDD per 1,000 inhabitants and per day. In 1992 123% more containers and 47.29% more DDD of calcitonins were used than in 1991. In February 1993, DDD consumption of calcitonins intranasally was twice the parenteral consumption. Pensioners consumed 77.63% of the DDD of parenteral calcitonins, compared with the active population; and 71.78% compared with intranasally taken calcitonins. CONCLUSIONS: The market introduction of intranasal methods has led to a notable increase in calcitonin consumption. Intranasal methods make up an ever-growing percentage of consumption and reached double the parenteral consumption in February 1993. By population groups, it was observed that pensioners used parenteral more than intranasal methods.

Administration, Intranasal↗

PubMed1976

Prolonged elevation of luteinizing hormone (LH) after intranasal administration of an analog of LH-releasing hormone.

[D-Leu-6,desGly-NH2-10]-LH-RH-ethylamide, an analog of luteinizing hormone-releasing hormone (LH-RH), was administered by intranasal spray or tube to 18 healthy men. A significant release of LH occurred within 15 minutes and was sustained for as long as 12 hours in what appeared to be a diphasic response. Both the spray and rhinyl tube were shown to be effective methods for releasing LH by intranasal administration of the LH-RH analog.

Administration, Intranasal↗

PubMed2005

Enhancement of systemic and CNS delivery of meptazinol hydrochloride by intranasal administration to rats.

AIM: To investigate the extent of systemic absorption and uptake of meptazinol (MEP) hydrochloride in cerebrospinal fluid (CSF) after intranasal administration on rats and compare with oral administration. METHODS: CSF samples were collected by a serial sampling method. The concentration of MEP in the biological samples was measured by HPLC with fluorescence detector. RESULTS: Rapid and significant levels of MEP in plasma and CSF can be achieved after nasal administration whereas the oral administration resulted in considerably lower drug concentrations. AUC in plasma and CSF from the nasal route are 7.375 and 15.6 folds compared with those of the oral route, respectively. CONCLUSION: Intranasal MEP is able to show quick absorption and improve the bioavailability, which could be a promising alternative to oral administration.

Administration, Intranasal↗

PubMed1987

Evaluation and significance of the degree of pituitary-gonadal inhibition during intranasal administration of buserelin.

In 12 patients (11 girls, 1 boy) with central precocious puberty and 4 patients (3 girls, 1 boy) with idiopathic short stature treated for 1 year with a GnRH superagonist, buserelin (0.3 mg intranasally, 4 times a day), a variable degree of inhibition of sex steroid secretion and pubertal development was observed. Regression of breast or genital development required a daily dosage of buserelin greater than or equal to 34 microgram/kg. After 3, 6, 9 and 12 months of treatment, the serum oestradiol level in the girls was positively related (r = 0.69) to basal serum LH measured at the same time and to change in breast development during the previous 3 months. In contrast, LH response to GnRH was very low in all the patients and not related to the degree of oestradiol inhibition. Height velocity and bone age velocity during the year of treatment showed no significant correlation with mean oestradiol level. Bone age velocity during treatment was inversely related to bone age at onset of buserelin. These data show that 1) the pituitary gonadal suppression during intranasal administration of buserelin is variable and dose-dependent; 2) gonadotropin response to GnRH is not a sensitive indicator of incomplete pituitary suppression during buserelin treatment; and 3) bone age velocity during treatment is more reduced the more advanced bone age is at onset of treatment.

Administration, Intranasal↗